PMID- 19380622
OWN - NLM
STAT- MEDLINE
DCOM- 20090604
LR  - 20220310
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 119
IP  - 17
DP  - 2009 May 5
TI  - Conventional dendritic cells at the crossroads between immunity and cholesterol 
      homeostasis in atherosclerosis.
PG  - 2367-75
LID - 10.1161/CIRCULATIONAHA.108.807537 [doi]
AB  - BACKGROUND: Immunoinflammatory mechanisms are implicated in the atherogenic 
      process. The polarization of the immune response and the nature of the immune 
      cells involved, however, are major determinants of the net effect, which may be 
      either proatherogenic or antiatherogenic. Dendritic cells (DCs) are central to 
      the regulation of immunity, the polarization of the immune response, and the 
      induction of tolerance to antigens. The potential role of DCs in atherosclerosis, 
      however, remains to be defined. METHODS AND RESULTS: We created a mouse model in 
      which the lifespan and immunogenicity of conventional DCs are enhanced by 
      specific overexpression of the antiapoptotic gene hBcl-2 under the control of the 
      CD11c promoter. When studied in either low-density lipoprotein receptor-deficient 
      or apolipoprotein E-deficient backgrounds, DC-hBcl2 mice exhibited an expanded DC 
      population associated with enhanced T-cell activation, a T-helper 1 and T-helper 
      17 cytokine expression profile, and elevated production of T-helper 1-driven 
      IgG2c autoantibodies directed against oxidation-specific epitopes. This 
      proatherogenic signature, however, was not associated with acceleration of 
      atherosclerotic plaque progression, because expansion of the DC population was 
      unexpectedly associated with an atheroprotective decrease in plasma cholesterol 
      levels. Conversely, depletion of DCs in hyperlipidemic CD11c-diphtheria toxin 
      receptor/apolipoprotein E-deficient transgenic mice resulted in enhanced 
      cholesterolemia, thereby arguing for a close relationship between the DC 
      population and plasma cholesterol levels. CONCLUSIONS: Considered together, the 
      present data reveal that conventional DCs are central to the atherosclerotic 
      process, because they are directly implicated in both cholesterol homeostasis and 
      the immune response.
FAU - Gautier, Emmanuel L
AU  - Gautier EL
AD  - INSERM UMR-S U939, Hopital de la Pitie, Paris, France.
FAU - Huby, Thierry
AU  - Huby T
FAU - Saint-Charles, Flora
AU  - Saint-Charles F
FAU - Ouzilleau, Betty
AU  - Ouzilleau B
FAU - Pirault, John
AU  - Pirault J
FAU - Deswaerte, Virginie
AU  - Deswaerte V
FAU - Ginhoux, Florent
AU  - Ginhoux F
FAU - Miller, Elizabeth R
AU  - Miller ER
FAU - Witztum, Joseph L
AU  - Witztum JL
FAU - Chapman, M John
AU  - Chapman MJ
FAU - Lesnik, Philippe
AU  - Lesnik P
LA  - eng
GR  - P01 HL088093/HL/NHLBI NIH HHS/United States
GR  - R01 HL086559/HL/NHLBI NIH HHS/United States
GR  - HL086559/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090420
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*etiology
MH  - Autoantibodies
MH  - Cell Proliferation
MH  - Cholesterol/*blood
MH  - Cytokines
MH  - Dendritic Cells/cytology/*immunology
MH  - Genes, bcl-2/genetics
MH  - Homeostasis
MH  - *Immunity
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Animal
EDAT- 2009/04/22 09:00
MHDA- 2009/06/06 09:00
CRDT- 2009/04/22 09:00
PHST- 2009/04/22 09:00 [entrez]
PHST- 2009/04/22 09:00 [pubmed]
PHST- 2009/06/06 09:00 [medline]
AID - CIRCULATIONAHA.108.807537 [pii]
AID - 10.1161/CIRCULATIONAHA.108.807537 [doi]
PST - ppublish
SO  - Circulation. 2009 May 5;119(17):2367-75. doi: 10.1161/CIRCULATIONAHA.108.807537. 
      Epub 2009 Apr 20.